Granulocyte colony-stimulating factor (G-CSF) is the standard growth factor for mobilizing hematopoietic progenitor cells in healthy peripheral blood progenitor cell (PBPC) donors. G-CSF is given daily for 5 days to PBPC donors prior collecting (PBPC) concentrates by apheresis. PBPC concentrate donors given G-CSF experience splenic enlargement and rarely, spontaneous rupture of the spleen. We evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and accessed factors effecting size changes. Healthy adults were given G-CSF (10 micrograms/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length prior to giving G-CSF, the day of apheresis, and 4 days after apheresis. Spleen length increased in 19 of 20 donors. On the day of apheresis the average length was 14% greater than before G-CSF and 4 days after PBPCs were collected spleen length was reduced in length, but remained greater than baseline levels. A second study was initiated to determine if spleen length returns to baseline levels 10 days after apheresis. Healthy adults were again given G-CSF (10 micrograms/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length prior to giving G-CSF, the day of apheresis, and 10 days after apheresis. Spleen length increased in 9 of 10 donors. Mean spleen length changed from 10.7 ? 1.1 cm pre-G-CSF to 12.0 ? 0.8 cm on the apheresis day. The mean increase in length was 1.4 ? 1.0 cm or 13.6 ? 10.9%. 10 days after apheresis the spleen length fell to 10.7 ? 1.1 cm and did not differ from baseline levels. For 8 of the 9 donors whose spleen length increased, the length measured 10 days after apheresis was within 0.5 cm of baseline length. In one donor spleen length remained 0.7 cm or 7% longer than baseline length 10 days after apheresis. This donor was a 23-year old Caucasian female whose spleen length on the apheresis day was 1.9 cm or 18% longer than baseline length. We found that spleen length increases in PBPC donors are transient and reversible. In most donors the spleen returned to normal size within 10 days. Future studies will focus on studying the use of a new long-acting form of G-CSF, polyethylene glycolated-G-CSF (PEG-G-CSF) to mobilized PBPCs in healthy donors. The optimum dose and safety of PEG-G-CSF will be studied.